Newsletter September 2013

Newsletter I
The Natural Killer Cell-­‐Based An;-­‐Cancer Immunotherapies -­‐NaturImmun-­‐ project is a Marie Curie Ini;al Training Network funded by the EC 7th Framework Program, Grant 317013. The network started in October 2012 and will run over 4 years. Mission of the project The main goal of this network is to generate new knowledge on the molecular mechanisms of innate immune responses against tumor-­‐ and virally infected cells focusing on NK and NKT cells. Our ambi;ous project NaturImmun aims to translate our findings into the development of cell-­‐based technologies and reagents in the treatment of cancer and viral infec;ons. As part of a Marie Curie program, we will also focus on the promo;on and recogni;on of excellence in European research, therefore we will highlight the personal achievements of our fellows with a view to suppor;ng their further development and interna;onal recogni;on. Par$cipants NaturImmun is formed by 11 groups located in 7 countries. All our PIs are renown scien;sts in the field of NK cells and we also count with 3 biotech/
pharmaceu;cal companies. Nine Early Stage Researchers (ESR or PhD students) and two Experienced Researchers (ER or postdocs) were selected aIer a very selec;ve fellow assessment to par;cipate in this ambi;ous project. Here an overview of our “NK Crew”: Group 1 2 3 4 5 6 Loca$on Vienna, Austria. Principal Inves$gator Fellow Postdoc Angélica Cuapio Mexico „Tumor-­‐invading NK subpopula;ons of NK cells and their ligands on tumor cells“ Coordinator Erhard Hofer Medical University Vienna Paris, France James di Santo Ins;tute Pasteur PhD student Silvia López Lastra Spain “Dis;nct NK subsets for therapy of human leukemias in HIS mice” Ofer Mandelboim Hebrew University PhD student Dominik Schmiedl Germany “miRNAs in tumor and virus-­‐infected cells controlling the NK response to tumors and viruses” Jerusalem, Israel Barcelona, Spain Cambridge, England Vienna, Austria Miguel López Botet University Pompeu Fabra John Trowsdale University of Cambridge Arndt von Haeseler University of Vienna PhD student Mirte Post Netherlands „Genera;on of tumor-­‐reac;ve popula;ons of NK cells from cord blood stem cells“ PhD student Aldi Pupuleku Albania “Coining of the NKR repertoire by human CMV and consequences for BMT in leukemia pa;ents” PhD student KaMria Van der Ploeg Netherlands “Modula;on of Ligands for Ac;va;ng Receptors on NK cells” PhD student Konstan$na Kyriakouli Greece “Detec;on of polymorphisms from next-­‐genera;on sequence data with focus on NKRs and their ligands“ Welcome to the first edi$on of Naturimmun NewsleMer! The aim of this Newslecer is to keep informed and updated all the members of NaturImmun about the mee;ngs, achievements from each partner, training ac;vi;es such as summer/winter schools,etc. It is a space open to all of you to contribute in the following numbers, so please send your comments and/or sugges;ons. Yours, Angélica Cuapio, the editor. Medical University Vienna Lazarecgasse 19A-­‐1090 Vienna, Austria [email protected] Background: An NK cell (yellow) acacking a cancer cell (red). Photo from Prof. Dr. Rupert Handgre;nger, Clinic for Children’s and Youth Medicine, University Hospital of Tübingen, Gemany Newsletter I
Group Loca$on Principal Inves$gator 7 London, England Amit Nathwani University College London 8 Hannover, Germany 9 Bergisch Gladbach, Germany Ulrike Köhl Hannover Medical School Volker Huppert Miltenyi Dirk Groenewegen Glycostem Therapeu;cs 10 Nijmegen, Netherlands Fellow PhD student Susanne Arthold Austria "Analysis of human induced pluripotent stem (iPS) cells for the study and treatment of hematopoie;c disorders" PhD student Oana Ciocarlie Romania "Immune recons;tu;on of dendri;c cells following allogeneic stem cell transplanta;on" PhD student María Delso Vallejo Spain “Development of technologies for isola;on and genera;on of large scale ac;vated therapeu;c NK cells PhD student John Veluchamy India “Development of technologies for isola;on and genera;on of large scale ac;vated therapeu;c NK cells” Jan Spanholtz Glycostem Therapeu;cs 11 Heidelberg, Germany Eugene Zhukovsky Affimed Therapeu;cs Mee$ng the NK fans For our first newslecer, we interviewed the group of the coordinator partner, Dr. Erhard Hofer in Vienna, Austria. The idea of this sec;on is to mo;vate the fellows with the experiences of the PIs and vice versa. It is also a means of knowing each other within the group since we will be working together for 4 years and in the future some of us will con;nue in the NK field. Lets make Naturimmun the friendly printed corner  All fellows and Pis will protagonize the up-­‐
coming numbers of the Naturimmun Newslecer, so get ready to surprise us! Interview to Erhard Hofer Erhard, what is the main topic(s) of research in your lab? We are interested to understand human NK cell differen;a;on, how tumors may modulate NK subsets and to see whether NK cells can be employed in tumor therapy. In an independent second project we analyze endothelial differen;a;on, progenitor cells and vasculariza;on. Postdoc Thorsten Gantke Germany „Bispecific reagents to redirect NK/T cell killing to leukemias and lymphomas" What mo$vated you to create/organize this huge European network of renown scien$sts and outstanding fellows that study a very specific cell type in cancer? We had a previous successful Marie Curie project between 2006 and 2009 and this project is based in part on results of the previous one, some partners have been in the previous consor;um What are your expecta$ons from this network? I hope that we will be able to gain important informa;on on NK cell / tumor interac;ons and thus to pave the way for successful NK cell therapy How is your current personal situa$on in Vienna? I like to be in Vienna, it is a city with many cultural ac;vi;es and recrea;on areas are close, my two sons live in Vienna and three grandchildren keep me busy on weekends What kind of music do you prefer to listen? And to dance? Do you play any musical instrument? Generally I like to listen to classical music such as Beethoven, I do however not play a musical instrument, my talent is more into visual arts, I like to visit museums etc. Background: An NK cell (yellow) acacking a cancer cell (red). Photo from Prof. Dr. Rupert Handgre;nger, Clinic for Children’s and Youth Medicine, University Hospital of Tübingen, Gemany Newsletter I
As a good Austrian, I bet you might be a master skier, am I wrong? Correct, skiing is s;ll my favorite sport, especially in deep powder snow If you were not a scien$st now, what would like to be? Hard to say now, maybe an architect or a photographer Finally, because now it is $me of lunch, what is your favorite Austrian dish? Could you give us an easy recipe from your home town? I am from Klagenfurt in the province Carinthia and there is a unique Carinthian dish called “Kärntner Nudel” I like to eat when I am there. It is a kind of ravioli, but a lot larger, filled with uniquely spiced curd cheeses. I can try to get the recipe. Holland to visit my boyfriend. I like the mul;culture in our lab, the amazing buildings in the city, the fantas;c public transport and how good you can go out for dinner for a good price. I don’t like the loads of forms you need to arrange things, the fact that Austrians are not used to bikers so I get almost run over a lot of ;mes and the some;mes bit unfriendly waiters/bartenders. My new hobbies are bicycling and my Dutch boyfriend. Interview to Mirte Post Mirte, why did you chose the project from Erhard? Because of all the projects I had the feeling it ficed to my interests and because I had a good connec;on from my side with Erhard. Can you briefly describe the aim of your project? To evaluate the role of the transcrip;on factor ZNF683 or Hobit in the differen;a;on of ex vivo cultured CD34+ to mature NK cells What and where did you study? Did you have professional experience on your new field before star$ng in Vienna? I studied Biomedical Sciences in Nijmegen, Holland. My master internship included FACS analysis and culture and I had some prac;cal experience in Western Blot and RT-­‐PCR. All the training lacked for virus produc;on and knock-­‐down or overexpression systems. Tell us how was your life before landing in Austria AIer my studies I worked 4 days a week in a hospital searching for pa;ent files for the doctors. One day I spend on job searching, sending applica;ons and trying to make new contacts in my fields of interest. In the weekends I went out, played hockey and relaxed with friends or my parents or my younger sister. How is your life in Vienna? What do you like and do not like? Do you have new hobbies? Now I work 5 days a week, once a month I meet other Dutch people in town, I play field hockey, try to bicycle on a racing bike once a week, go out, do fun things with friends or fly to The NKillers Background: An NK cell (yellow) acacking a cancer cell (red). Photo from Prof. Dr. Rupert Handgre;nger, Clinic for Children’s and Youth Medicine, University Hospital of Tübingen, Gemany Newsletter I
How has it been to speak a new language and integrate into your new society? Austrian German was really easy for me to learn, one because it is quite similar to Dutch and two I learn languages quite fast. Especially on the field hockey field I no;ced the difference once they found out I spoke German fast. The integra;on in the team was a lot becer aIer that. Also Austrians seem a bit more open if you at least make an acempt to speak Austrian German. Finally, How do you see yourself in 4 years? As doctor M. Post, giving a good party to celebrate my promo;on and gewng ready to move back to Holland. But I will probably have to finish all the experiments and the wri;ng most of the part of the 4th year. Interview to Angélica Cuapio Angélica, what aMracted you from the posi$on offered by Erhard? First, when I applied, I was very intrigued by the fact that there was a big network working specifically on NK cells. Secondly, since I read about Erhard´s project, I felt myself like fish in the water because I could understand every single word of the project and also because Erhard and his group were nice people. Can you briefly describe what you will do in your project? Yes, based on an ex vivo differen;a;on method to obtain NK cells from hematopoie;c stem cells, I will study the role of the transcrip;on factor MEF2C in the development of NK cells. In a parallel project, I will characterize the NK cell subsets in hematological malignancies (lymphoma or leukemia) as well as in solid tumors (colorectal cancer) to determine the effect of NK cells on tumors and also the other way round, what is the effect of tumor cells on NK cells. What is your academic forma$on and previous experience before star$ng at Erhard´s lab? I studied Medicine in Mexico City, and immediately aIer I did my PhD in Germany as a Marie Curie fellow. I studied the immunoregulatory role of CD56 bright NK cells in mul;ple sclerosis, therefore my interest on these cells increased. What are your expecta$ons from Naturimmun acer finishing your postdoc? I had a great experience being a Marie Curie fellow, I could meet people from diverse fields of research but all emerging in one single aim, the study of mul;ple sclerosis. I find this principle very fundamental in the new horizons of doing research, bringing people from different scien;fic fields to generate new knowledge and approaches from different p e r s p e c ; v e s t o s o l v e s i n g l e p r o b l e m s . Now I have again the great opportunity to be in an Interdisciplinary group from which I expect to find together with all the partners new answers on the biology of NK cells and possible applica;ons of these cells in the treatment of that horrible en;ty called cancer. How was your personal life before coming to Vienna and how is it currently? I was living in Hamburg, Germany for the last 4 years with my boyfriend Felix. He is german, we met during our social service in Mexico, he is a doctor as well. We lived two years in Mexico, then 4 in Germany and now we live in different countries… finally we can breath! No, just kidding. By fortune he will move to Vienna next year  In Vienna I have now several friends, mainly ar;sts and musicians, that is something I love from Vienna, all these ar;s;c environments. Just as an example, my roommate has 3 pianos in his room! Angélica, what is your favorite kind of music and or sports? I love postrock music. I have had the chance this year to acend to several concerts and fes;vals, gewng to know closer the musicians, but I just want to declare: Im not a groupie! I just enjoy this music and people in those worlds ;-­‐) For those interested, Postrock is a rock subgenre that uses rock instrumenta;on for non-­‐rock purposes, it is very common the use of guitars as facilitators of ;mbres and textures rather than riffs and powerchords. I definetely suggest you to explore this kind of music, and who knows, maybe at some point some of us will be mee;ng in some fes;vals… Here some of my favorite bands: My Sleeping Karma, Caspian, And So I Watch You From Afar. Have fun! Regarding sports, I love swimming. My dad was the promoter, he put me into rivers since I was 1 year old (there are many pics that prove it, not only the stories of grandparents). During my adolescence, I was part of the mexican pre-­‐olympic swimming team, but I was a bit lazy to con;nue… I s;ll keep on swimming by my own trying to improve my bucerfly stroke, which has always been my Achilles´heel. Background: An NK cell (yellow) acacking a cancer cell (red). Photo from Prof. Dr. Rupert Handgre;nger, Clinic for Children’s and Youth Medicine, University Hospital of Tübingen, Gemany Newsletter I
SUMMER SCHOOL 1 / 2nd CONSORTIUM MEETING EC Ini$al Training Network FP7-­‐PEOPLE-­‐ 2012-­‐ITN-­‐317013 “NATURIMMUN” September 1-­‐9, 2013 University of Cambridge Sunday, September 1 Arrival of students at Corpus Chris; College. Trumpington St, Cambridge CB2 1RH, UK (Breakfast will be at Corpus Chris; College) Contact: Kacria Van Der Ploeg [email protected] Tel. +44 79059 42234 Monday, September 2, 9 AM, -­‐ Friday, September 6, 5 PM Bioinforma$cs Course: • Venue: IT training room, Department of Gene;cs, University of Cambridge (5 min walk) Link to program: • hMp://www.ebi.ac.uk/training/course/bioinforma$cs-­‐resources-­‐immunologists Friday, September 6 Arrival of PIs at King’s College, Cambridge (Breakfast will be at Corpus Chris; College) King's Parade, Cambridgeshire CB2 1ST, UK Contact: Kacria Van Der Ploeg Saturday, September 7 Venue: Lesley Stephens room at Trinity Hall (5 min walk) 9.00 -­‐ 9:15 John Trowsdale (University of Cambridge) Erhard Hofer, Coordinator (Medical University Vienna) Welcome & Introduc$on Scien;fic Workshop Module 1: NK cell ac$vity and regula$on 09:15 – 09:45 Miguel Lopez-­‐Botet (Universitat Pompeu Fabra) Specific project overviews of PIs and project proposals/reports of Marie Curie fellows (10´ report and 5´ discussion) 9:45 – 10:00 10:00 – 10:15 10:15 – 10:30 10:30 – 10:45 10:45– 11:00 11:00 – 11:15 11:15 – 11:30 11:30 – 11:45 „Coining of the NK cell receptor repertoire by human CMV“ Miguel Lopez-­‐Botet Universitat Pompeu Frabra Diogo Baia Aldi Pupuleko Coffee break „Control of ex vivo differen$a$on of NK cells & subsets in tumours“ Erhard Hofer Medical University Vienna Markus Osl Angélica Cuapio Gómez Mirte Post 11:45 – 12:00 12.00 – 12:15 12.15– 12:30 12:30– 12:45 „NK cell subsets important for leukemia therapy & HIS mouse models“ James di Santo Ins;tute Pasteur, Paris Silvia Lopez Lastra „iPS cells for the study and treatment of haematopoe$c disorders“ Amit Nathwani University College London Susanne Arthold 12:45– 14:00 Lunch Background: An NK cell (yellow) acacking a cancer cell (red). Photo from Prof. Dr. Rupert Handgre;nger, Clinic for Children’s and Youth Medicine, University Hospital of Tübingen, Gemany Newsletter I
***CuHng Edge Lectures *** (45´and 15´discussion) 14:00 – 15.00 James di Santo Ins;tute Pasteur, Paris Innate Lymphoid Cells: Diversifica$on and Func$on 15:00 – 16:00 Ashley MoffeM University of Cambridge The role of NK cells in human reproduc$ve success 16:00 – 16:15 Coffee Break 16:15 – 17:15 Francesco Colucci University of Cambridge 17:15 – 18:15 Francisco Borrego BioCruces Health Research Ins;tute Barakaldo, Spain 19:00 Allorecogni$on in transplanta$on and reproduc$on Role of NK cells in the mechanism of ac$on of therapeu$c an$bodies Joint Dinner at Trinity Hall Sunday, September 8th Venue: Lesley Stephens room at Trinity Hall Scien;fic Workshop Module 2: Genomics of NKR loci 09:00 – 09:30 John Trowsdale (University of Cambridge) Specific project overviews of PIs and project proposals/reports of Marie Curie fellows (10´ report and 5´ discussion) 09:30 – 09:45 09:45 – 10:00 10:00– 10:15 10:15 – 10:30 10:30 – 10:45 10:45– 11:00 „Gene$cs of NKRs in rela$on to disease suscep$bility“ John Trowsdale University of Cambridge Kacria Van de Ploeg Anna Gawedzka Shirin Ashraf Coffee break „Detec$on of polymorphisms from next-­‐genera$on sequence data with focus on NKRs and their ligands“ Arndt Von Haeseler Medical University Vienna 11:00 – 11:15 11:15– 11:30 „miRNA control of NK cell response to tumours and viruses“ Ofer Mandelboim Hebrew University, Jerusalem Dominik Schmiedl 11:30– 11:45 11:45 – 12:00 „NK cells for the treatment of leukemia and other tumours“ Ulrike Köhl Medical University of Hannover Oana Ciorcalie 12:00 – 13:15 Lunch Background: An NK cell (yellow) acacking a cancer cell (red). Photo from Prof. Dr. Rupert Handgre;nger, Clinic for Children’s and Youth Medicine, University Hospital of Tübingen, Gemany Newsletter I
13:15 – 13:30 13:30 – 13:45 13:45 – 14:00 14:00 – 14:30 Technology for isola$on and genera$on of clinical scale NK cells Volker Huppert Miltenyi Biotec, Bergisch Gladbach Markus Granzin Chris;an Egler-­‐Wedeking Maria Delso Vallejo 14:30 – 14:45 Clinical scale ex vivo genera$on of NK cells from cord blood haematopoe$c stem cells Jan Spanholtz / Dirk Groenewegen Glycostem Therapeu;cs, Nijmegen 14:45 – 15.00 15:00 – 15:15 Bispecific reagents to redirect NK cell killing to leukemia and lymphoma Eugene Zhukovsky Affimed Therapeu;cs, Heidelberg Thorsten Gantke 15:15 – 15:30 15:30 – 16:30 All PIs and fellows Discussion of major joint collabora;ons Which leukemia/carcinoma as priority targets Which NK subset as priority effectors Which an;gens as priority targets Which priority animal models for evalua;on of NK cells and reagents 16:30 – 17:30 All PI´s All fellows Supervisory Board Mee;ng III Mee;ng of fellows 17:30 – 18:00 All PI´s and fellows Joint discussion 18:00 – 19:00 As needed Discussions of individual collabora;ons 19:00 Coffee Break Joint dinner Monday, September 9th Departure SAVE THE DATES 17-­‐21. Sept, 2013 17. Sept.2013 18-­‐21 Sept.2013 NK2013 14th Mee;ng of the Society for Natural Immunity Heidelberg, Germany. Workshop: NK cells in clinical applica;on experiences and perspec;ves The workshop is an ini;a;ve by Miltenyi Biotec and will focus on current progress in NK cell applica;ons in clinical sewngs NK2013 Mee;ng Take note: Ulrike Köhl, Jan Spanholtz and Ofer Mandelboim are special speakers in the mee;ng. More info at: hcp://www.nk2013.com Background: An NK cell (yellow) acacking a cancer cell (red). Photo from Prof. Dr. Rupert Handgre;nger, Clinic for Children’s and Youth Medicine, University Hospital of Tübingen, Gemany Newsletter I
Sec$on: Go for it! In this sec;on we will communicate your latest publica;ons, grants, awards, patents, invited lectures and/or any measure of esteem. You are the ones building this sec;on, please let us know all your achievements. Congratula;ons to all our partners! JAMES DI SANTO AWARDS • Dis;nguished Alumnus Award, Weill Cornell Graduate School of Medical Sciences (2013) • Dis;nguished Immunologist Award, University of Alberta (2013) GRANTS • EU – FP7 : « PathCo » (par;cipant ; coordinated by W. Paxton, AMC) ANRS : Humanized mouse consor;um (co-­‐organizer) PUBLICATIONS • Spits, H., Ar;s, D., Colonna, M., Diefenbach, A., Di Santo, J.P., Eberl, G., Koyasu, S., Locksley, R.M., McKenzie, A.N.J., Mebius, R.E., Powrie, F. and Vivier, E. (2013) Innate Lymphoid Cells -­‐ a proposal for uniform nomenclature. Nature Reviews Immunology 13 :145-­‐149. • García-­‐Ojeda, M.E., Klein Wolterink, R.G.J., Lemaitre, F., Richard-­‐Le Goff, O., Hasan, M., Hendriks, R.W., Cumano, A. and Di Santo, J.P. (2013) GATA-­‐3 promotes T cell specifica;on by repressing B cell poten;al in pro-­‐T cells in mice. Blood 121:1749-­‐1759. • Vosshenrich, C.A.J. and Di Santo, J.P. (2013) Developmental programming of natural killer and innate lymphoid cells. Current Opinion in Immunology 25:130-­‐138. • Klein Wolterink, R.G.J., Serafini, N., van Nimwegen, M.,Vosshenrich, C.A.J., Fonseca Pereira, D., Veiga-­‐Fernandes, H., Hendriks, R.W. and Di Santo, J.P. (2013) Essen;al, dose-­‐dependent role for the transcrip;on factor Gata3 in the development of IL-­‐5+ and IL-­‐13+ type 2 innate l ymphoid cells. Proceedings of the Na;onal Academy of Sciences (USA) 110:10240-­‐10245. • Ribeiro, A.R., Rodrigues, P.M., Meireles, C., Di Santo, J.P. and Alves, N.L. (2013) Thymocyte selec;on regulates the homeostasis of IL-­‐7-­‐ expressing thymic cor;cal epithelial cells in vivo. The Journal of Immunology 191:1200-­‐1209. • Guy-­‐Grand, D., Vassalli, P., Eberl, G., Pereira, P., Burlen-­‐Defranoux, O., Lemaitre, F., Di Santo, J.P., Freitas, A.A., Cumano, A. and Bandeira, A. (2013) Origin, hemolympha;c cycle and intraepithelial fate of gut tropic T cells. Journal of Experimental Medicine 210:1839-­‐1854. • Albanesi, M., Mancardi, D.A., Jönsson, F., Iannascoli, B., Fiece, L., Di Santo, J.P., Lowell, C.A. and Bruhns, P. (2013) Neutrophils mediate an;body-­‐induced an;-­‐tumor effects in mice. Blood (in press). MIGUEL LÓPEZ BOTET GRANTS • Evalua;on of NK cell contribu;on to chronic kidney allograI rejec;on in response to HLA-­‐specific alloan;bodies, gene;c mismatch and CMV infec;on. La Marató TV3 Founda;on (2013-­‐2015). PUBLICATIONS • Muntasell A, López-­‐Montañés M, Vera A, Heredia G, Romo,Peñafiel J, Moraru M, Vila J, Vilches C, López-­‐Botet M. NKG2C Zygosity Influences CD94/NKG2C Receptor Func;on and the NK-­‐cell Compartment Redistribu;on in Response to Human CMV. Eur J Immunol (in press) • Muntasell A, Vilches C, Angulo A, López-­‐Botet M. Adap;ve reconfigura;on of the human NK-­‐cell compartment in response to cytomegalovirus: a different perspec;ve of the host-­‐pathogen in-­‐ terac;on. Eur J Immunol. 2013; 43:1133. • Muntasell A, Costa-­‐Garcia M, Vera A, Marina-­‐García N, Kirschning CJ, López-­‐Botet M. Priming of NK cell an;-­‐viral effector mechanisms by direct recogni;on of human cytomegalovirus. Front Immunol 2013; 4:40. • Solana R, Tarazona R, Aiello AE, Akbar AN, Appay V, Beswick M, Bosch JA, Campos C, Can;sán S, Cicin-­‐Sain L, Derhovanessian E, Ferrando-­‐Mar„nez S, Frasca D, Fulöp T, Govind S, Grubeck-­‐ Loebenstein B, Hill A, Hurme M, Kern F, Larbi A, López-­‐Botet M, Maier AB, McElhaney JE, Moss P, Naumova E, Nikolich-­‐Zugich J, Pera A, Rector JL, Riddell N, Sanchez-­‐Correa B, Sansoni P, Sauce D, van Lier R, Wang GC, Wills MR, Zieliński M, Pawelec G. CMV and Immuno-­‐ senescence: from basics to clinics. Immun Ageing. 2012; 9:23. • Mar„nez-­‐Pomar N, Lanio N, Romo N, López-­‐Botet M, Matamoros N. Func;onal impact of A91V muta;on of the PRF1 perforin gene. Hum Immunol. 2013; 74:14. • Cisneros E, Moraru M, Gómez-­‐Lozano N, López-­‐Botet M, Vilches C. KIR2DL5: An Orphan Inhibitory Receptor Displaying Complex Pacerns of Polymorphism and Expression. Front Immunol. 2012; 3:289. CONFERENCES Interna;onal Congress of Immunology (ICI-­‐2013) “Reconfigura;on of the NK cell compartment by human cytomegalovirus Infec;on” (Milano, 2013) Background: An NK cell (yellow) acacking a cancer cell (red). Photo from Prof. Dr. Rupert Handgre;nger, Clinic for Children’s and Youth Medicine, University Hospital of Tübingen, Gemany Newsletter I
• Noyola DE, Fortuny C, Muntasell A, Noguera-­‐Julian A, Muñoz-­‐ Almagro C, Alarcón A, Juncosa T, Moraru M, Vilches C, López-­‐Botet M. Influence of congenital human cytomegalovirus infec;on and the NKG2C genotype on NK-­‐cell subset distribu;on in children. Eur J Immunol. 2012; 42:3256. • Tallerico R(s), Todaro M(s), Di Franco S(s), Maccalli C(s), Garofalo C(s), Sowle R(s), Palmieri C(s), Tirinato L(s), Pangigadde PN(s), La Rocca R(s), Mandelboim O(CO), Stassi G(s), Di Fabrizio E(s), Parmiani G(s), Moreca A(CO), Dieli F(s), Kärre K(CO), Carbone E(PI). Human NK cells selec;ve targe;ng of colon cancer-­‐ini;a;ng cells: a role for natural OFER MANDELBOIM cytotoxicity receptors and MHC class I molecules. J Immunol. 2013 Mar 1;190(5):2381-­‐90. doi: 10.4049/jimmunol.1201542. Epub 2013 GRANTS • The Israel Science Founda;on and JDRF. NK cells and diabetes development. 250,000 shekels for one year. 1.10.212-­‐1.10.2013 • ERC advanced grant-­‐ERC. Recogni;on of bacteria by NK cells. 2,500000 Euro total. 1.2.2013-­‐1.2.2018 PUBLICATIONS • Tsukerman P(s), Stern-­‐Ginossar N(s), Gur C(s), Glasner A(s), Nachmani D(s), Bauman Y(s), YaminR(s), Vitenshtein A(s), Stanietsky N(s), Bar-­‐Mag T(s), Lankry D(s), Mandelboim O(PI). MiR-­‐10b downregulates the stress-­‐induced cell surface molecule MICB, a cri;cal ligand for cancer cell recogni;on by natural killer cells. Cancer Res. 2012 Aug 21.[Epub ahead of print]. • Gruda R(s), Brown AC(s), Grabovsky V(s), Mizrahi S(s), Gur C(s), Feigelson SW(s), Achdout H(s), Bar-­‐On Y(s), Alon R(CO), Aker M(CO), Davis DM(CO), Mandelboim O(PI). Loss of kindlin-­‐3 alters the threshold for NK cell ac;va;on in human leukocyte adhesion deficiency-­‐III. Blood. 2012 Nov 8;120(19):3915-­‐24. doi: 10.1182/blood-­‐2012-­‐02-­‐410795. Epub 2012 Sep 14. • Corrales-­‐Aguilar E(s), Trilling M(s), Reinhard H(s), Mercé-­‐Maldonado E(s), Widera M(s), Schaal H(s), Zimmermann A(T), Mandelboim O(CO), Hengel H.A(PI). novel assay for detec;ng virus-­‐specific an;bodies triggering ac;va;on of Fcγ receptors. J Immunol Methods. 2013 Jan 31;387(1-­‐2):21-­‐35. doi: 10.1016/j.jim.2012.09.06. Epub 2012 Sep 27. • Sela HY(s), Goldman-­‐Wohl DS(CO), Haimov-­‐Kochman R(CO), Greenfield C(s), Natanson-­‐Yaron S(s), Hamani Y(s), Revel A(s), Lavy Y(s), Singer O(s), Yachimovich-­‐Cohen N(s), Turetsky T(s), Mandelboim O(CO), Reubinoff B(CO), Yagel S(PI). Human trophectoderm apposi;on is regulated by Interferon γ-­‐induced protein 10 (IP-­‐10) during early implanta;on. Placenta. 2013 Mar;34(3):222-­‐30. doi: 10.1016/j.placenta 2012.12.008. Epub 2013 Jan 8. • Alvarez-­‐Breckenridge CA(s), Yu J(s), Price R(s), Wojton J(s), Pradarelli J(s), Mao H(s), Wei M(s), Wang Y(s), He S(s), Hardcastle J(s), Fernandez Jan 23. • Elboim M(s), Grodzovski I(s), Djian E(s), Wolf DG(CO), Mandelboim O(PI). HSV-­‐2 specifically down regulates HLA-­‐C expression to render HSV-­‐2-­‐infected DCs suscep;ble to NK cell killing. PLoS Pathog. 2013 Mar;9(3):e1003226. doi: 10.1371/journal.ppat.1003226. Epub 2013 Mar 28. • Bar-­‐On Y(s), Glasner A(s), Meningher T(s), Achdout H(s), Gur C(s), Lankry D (s) , Vitenshtein A (s) , Meyers AF (CO) , Mandelboim M (CO) , Mandelboim O (PI) . Neuraminidase-­‐mediated, NKp46-­‐ dependent immune-­‐evasion mechanism of influenza viruses. Cell Rep. 2013 Apr 25;3(4):1044-­‐50. doi: 10.1016/j.celrep.2013.03.034. Epub 2013 Apr 18. • Lankry D(s), Rovis TL(s), Jonjic S(CO), Mandelboim O(PI). The interac;on between CD300a and phospha;dylserine inhibits tumor cell killing by NK cells. Eur J Immunol. 2013 May 3. doi: 10.1002/eji. 201343433. [Epub ahead of print] • Stanietsky N(s), Rovis TL(s), Glasner A(s), Seidel E(s), Tsukerman P(s), Yamin R(s), Enk J(s), Jonjic S(CO), Mandelboim O(PI). Mouse TIGIT inhibits NK-­‐cell cytotoxicity upon interac;on with PVR. Eur J Immunol. 2013 May 15. doi: 10.1002/eji.201243072. [Epub ahead of print] • Hosomi S(s), Chen Z(s), Baker K(s), Chen L(s), Huang YH(s), Olszak T(s), Zeissig S(s), Wang JH(s), Mandelboim O(CO), Beauchemin N(CO), Lanier LL(CO), Blumberg RS(PI). CEACAM1 on ac;vated NK cells inhibits NKG2D-­‐mediated cytoly;c func;on and signaling. Eur J Immunol. 2013 May 22. doi: 10.1002/eji.201242676. [Epub ahead of print] • Ghadially H(s), Horani A(s), Glasner A(s), Elboim M(s), Gazit R(s), Shoseyov D(CO), Mandelboim O(PI). NKp46 regulates allergic responses. Eur J Immunol. 2013 Jul 23. doi: 10.1002/eji.201343388. [Epub ahead of print] REVIEWS SA(s), Kaur B(s), Lawler SE(s), Vivier E(CO), Mandelboim O(CO), Moreca A(CO), Caligiuri MA(PI), Chiocca EA(PI). NK cells impede glioblastoma virotherapy through NKp30 and NKp46 natural cytotoxicity receptors. Nat Med. 2012 Dec;18(12):1827-­‐34. doi: 10.1038/nm. 3013. Epub 2012 Nov 25. • Tsukerman P(s), Enk J(s), Mandelboim O(PI). Metastamir-­‐mediated I mmune evasion: miR-­‐10b downregulates the stress-­‐induced molecule MICB, hence avoid recogni;on by NKG2D receptor. Oncoimmunology. 2013 Jan 1;2(1):e22245. Background: An NK cell (yellow) acacking a cancer cell (red). Photo from Prof. Dr. Rupert Handgre;nger, Clinic for Children’s and Youth Medicine, University Hospital of Tübingen, Gemany Newsletter I
• Koch J(PI), Steinle A(PI), Watzl C(PI), Mandelboim O(PI). Ac;va;ng natural cytotoxicity receptors of natural killer cells in cancer and Infec;on. Trends Immunol. 2013 Apr;34(4):182-­‐91. doi: 10.1016/j.it. 2013.01.003. Epub 2013 Feb 13. CONFERENCES • Chairing the workshop en;tled: “Micro RNA” Sept. 2012 3rd European Congress of Immunology – ECI 2012, Glasgow, Scotland, • Regulatory Role of small RNA on September 12,13 2012, The Weizmann Ins;tute of Science. • NK cell Symposium 2012. Sept. 2012 German Cancer Research Center in Heidelberg. • IItalian Society of Immunology (SIICA) Retreat SUD October 2012, University of Magna Graecia Catanzaro • Tumor Immunology meets Oncology IX. May, 2013. Halle, Germany • 27th EFI conference "Immune evasion: A hide and seek game between host and pathogens-­‐ Networking in Immunogene;cs” • Schmidt S, Zimmermann SY, Tramsen L, Koehl U, Lehrnbecher T. Natural Killer Cells and An;fungal Host Response. Clin Vaccine Immunol Apr;20(4):452-­‐8. doi: 10.1128/CVI.00606-­‐12. (2013). • Heinze A, Elze MC, Kloess S, Ciocarlie O, Königs C, Betz S, Bremm M, Esser R, Klingebiel T, Serban M, Hucon JL, Koehl U. Age-­‐matched dendri;c cell subpopula;ons reference values in childhood. Scand J Immunol. Mar;77(3):213-­‐20. doi: 10.1111/sji.12024 (2013). • Koehl U, Brehm C, Huenecke S, Zimmermann SY, Kloess S, Bremm M, Ullrich E, Soerensen J, Quaiser A, Erben S, Wunram C, Gardlowski T, Auth E, Tonn T, Seidl C, Meyer-­‐Monard S, Stern M, Passweg J, Klingebiel T, Bader P, Schwabe D, Esser R. Clinical grade purifica;on and expansion of NK cell products for an op;mized manufacturing protocol. Front Oncol. 2013 May 17;3:118. doi: 10.3389/fonc. 2013.00118. . May 2013. Maastricht, Netherlands • XII Interna;onal Congress of Reproduc;ve Immunology hosted by Thanks for your contribu;ons! ASRI. June 2013, Boston, MA, USA • 1st Broad-­‐Israel Circuit SymposiumJune 2013. Mishkenot Sha'ananim, Israel. • Cancer Research Club, June 2013, Weizmann Ins;tute, Rehovot, Israel. ULRIKE KÖHL PUBLICATIONS • Stern M, Passweg RJ, Meyer-­‐Monard S, Esser R, Tonn T, Soerensen J, Paulussen M, Gratwohl A, Klingebiel T, Bader P, Tichelli A, Schwabe D, Köhl U. Preemp;ve Immunotherapy with Purified Natural Killer Cells aIer Haploiden;cal Stem Cell Transplanta;on. A Prospec;ve Phase II Study in 2 Centers. Bone Marrow Transplanta;on 48(3): 433-­‐8. doi: 10.1038/bmt.2012 (2013) • Schmidt S, Tramsen L, Perkhofer S, Lass-­‐Flörl C, Hanisch M, Röger F, Klingebiel T, Koehl U, Lehrnbecher T. Rhizopus oryzae hyphae are damaged by human natural killer (NK) cells, but suppress NK cell mediated immunity. Immunobiology. Immunobiology. 218(7):939-­‐44. doi: 10.1016/j.imbio.2012.10.013 (2013). • Reiners K, Kessler J, Rothe A, Hansen H, Hucke C, Reusch U, Koehl U, Duerkop H, Engert A, Sauer M, Pogge von Strandmann E. Rescue of impaired NK cell ac;vity in Hodgkin lymphoma with bispecific an;bodies in vitro and in pa;ents, Mol Therapy Apr;21(4):895-­‐903. doi: 10.1038/mt.2013.14. Epub 2013 Mar 5 (2013). How fellows think a PhD will be How a PhD really is... See you in the next number Background: An NK cell (yellow) acacking a cancer cell (red). Photo from Prof. Dr. Rupert Handgre;nger, Clinic for Children’s and Youth Medicine, University Hospital of Tübingen, Gemany